non invasive prenatal testing of down syndrome

Conditions: Down Syndrome

Summary: this is a randomized controlled trial in women at risk following combined prenatal screening for down syndrome. women will be asked about their preferences between nipt and routine prenatal diagnosis based on a dedicated questionnaire. women will then be randomized between nipt and standard invasive prenatal diagnosis.

this is a randomized controlled trial in women at risk following combined prenatal screening for down syndrome. women will be asked about their preferences between nipt and routine prenatal diagnosis based on a dedicated questionnaire. women will then be randomized between nipt and standard invasive prenatal diagnosis. the general objectives are : * promote the rapid and large implementation of non invasive prenatal testing (nipt) for down syndrome. * improve the management of women at risk after combined first trimester screening and reduce the number of invasive procedures and induced miscarriages . * evaluate nipt medically (in reducing the rate of invasive sampling and related complications, diagnostic performance and feasibility and acceptability in routine practice) and based on cost-analysis in comparison with standard invasive prenatal diagnosis currently proposed . * clarify the conditions of implementation and dissemination of nipt in the overall organization of prenatal screening for trisomy 21 (and provide data to later adjust or not the combination of tests and thresholds). promote the organization as networks of professionals involved in prenatal screening for trisomy 21 in order to allow the emergence of a national system of collection of outcomes to improve the quality of practices the main judgement criteria are: * main: - percentage of fetal loss in each group * secondary: * percentage of invasive tests in each group (amniocentesis or chorionic villus sampling ) * diagnostic performance of nipt , in particular false positive and negative * percentage of results within 3 weeks and average time interval for results of nipt * percentage of inconclusive results of dpani * percentage of other anomalies discovered at invasive sampling * percentage of invasive samples taken despite normal nipt (either because of later ultrasound anomaly or for maternal reinsurance) * association between maternal characteristics ( weight, height, parity , previous history , serum markers ... ) and the results of nipt * cost analysis of nipt in routine clinical practice the study will include 2450 high risk women in order to be powered enough to detect a 1% reduction of miscarriages in the group undergoing nipt instead of routine invasive prenatal diagnosis.

Eligibility criteria:
inclusion criteria: * pregnant women over 18 * at risk for down syndrome\> 1/250 based on combined screening using ultrasound together with maternal serum markers and prior to fetal karyotyping * singleton pregnancy * pregnancy between 11sa et 18sa * willing a fetal karyotype exclusion criteria: * risk for down syndrome\ 1/5 * nt\> 3 mm, papp-a or beta hcg \ 5 mom * multiple pregnancy , vanishing twin * morphological abnormalities at us * kown chromosomal anomaly in parents * patients not willing a fetal karyotype

Keywords: down, trisomy 21 nipt amniocentesis miscarriage invasive prenatal screening.